Topical composition, topical composition precursor, and methods for manufacturing and using

ABSTRACT

A tropical composition is provided. The topical composition can be prepared by diluting a topical composition precursor with water and adding additional components, if desired. The topical composition precursor can be prepared by melt processing a hydrophobic polymer composition that includes repeating pyrrolidone/alkylene groups wherein the alkylene groups contain at least 10 carbon atoms, and a hydrophilic polymer composition including repeating carboxylic groups and/or repeating hydroxyl groups. A topical composition precursor and methods for manufacturing and using a topical composition are provided by the invention.

FIELD OF THE INVENTION

The invention relates to a topical composition, a topical compositionprecursor, and methods for manufacturing and using the topicalcomposition and the composition precursor.

BACKGROUND OF THE INVENTION

Naturally occurring and synthetic polymers have been used inpharmaceutical and cosmetic preparations for several decades. Polymersthat have been used in pharmaceutical and cosmetic preparations includehydrophilic polymers, hydrophobic polymers, and polymers havinghydrophilic and hydrophobic properties. Hydrophilic polymers are oftenused as thickeners and/or film formers. Hydrophobic polymers are oftenused because of their ability to hold active ingredients and to bind toskin.

Compositions have been developed for enhancing the cutaneous penetrationof topically or transdermally delivered pharmacologically active agents.For example, see U.S. Pat. Nos. 5,045,317; 5,051,260; and 4,971,800.

SUMMARY OF THE INVENTION

A topical composition, a topical composition precursor, and methods formanufacturing and using a topical composition and a topical compositionprecursor are provided by the invention. The topical composition can bereferred to as a “delivery system” when it is used to promote thedelivery of active ingredients to skin tissue. When provided as a usesolution, the topical composition has an ability to adhere or bind toskin tissue and thereby hold active ingredients in proximity to skintissue. In addition, the topical composition has an ability to hold orcontain active ingredients so that the active ingredients can be madeavailable to skin tissue when the topical composition is applied to skintissue. Active ingredients that can be used include natural andsynthetic substances that produce a desired effect when placed on skintissue and may include medicines or drugs or other substances intendedfor the diagnosis, cure, mitigation, treatment, or prevention of adisease or condition, and may include substances that may becharacterized as protectants, repellants, and moisturizers.

The topical composition precursor of the invention can be provided as aresult of melt processing a hydrophobic polymer composition and ahydrophilic polymer composition in the presence of less than about 1 wt.% water. The hydrophobic polymer composition includes apoly(vinylpyrrolidone/alkylene) polymer wherein the alkylene groupcontains at least about 10 carbon atoms. The hydrophilic polymercomposition includes at least one of a hydrophilic polymer comprisingrepeating carboxylic acid groups and/or repeating hydroxyl groups.Exemplary hydrophilic polymers include polyacrylic acid having a weightaverage molecular weight of at least about 50,000 and exhibiting lessthan 1% cross-linking, poly(maleic acid/methylvinylether) copolymerhaving a weight average molecular weight of at least about 50,000,starch, derivatives of starch, cellulose, derivatives of cellulose,carboxymethyl cellulose, polyvinyl alcohol, cyclodextrins, dextrans, andmixtures thereof. The hydrophilic polymer composition can includepolyacrylic acid having a weight average molecular weight of betweenabout 50,000 and about 4,000,000, and exhibits less than 1%cross-linking and/or poly(maleic acid/methylvinylether) copolymer havinga weight average molecular weight of between about 50,000 and about4,000,000.

The hydrophobic polymer composition can include a mixture of differentpoly(vinylpyrrolidone/alkylene) polymers. When the hydrophobic polymercomposition contains a mixture of two differentpoly(vinylpyrrolidone/alkylene) polymers, the firstpoly(vinylpyrrolidone/alkylene) polymer can be provided at aconcentration of between about 5 wt. % and about 54 wt. %, based on theweight of the hydrophobic polymer composition. In addition, the secondpoly(vinylpyrrolidone/alkylene) polymer can be provided at aconcentration of between about 46 wt. % and about 95 wt. %, based on theweight of the hydrophobic polymer composition. Exemplarypoly(vinylpyrrolidone/alkylene) polymers includepoly(vinylpyrrolidone/1-eicosene) polymer andpoly(vinylpyrrolidone/hexadecene).

The topical composition precursor can be formed by mixing thehydrophobic polymer composition and the hydrophilic polymer compositionin a melt and providing a functional group parity between thepyrrolidone groups of the hydrophobic polymer composition and thecombination of carboxylic acid groups and/or hydroxyl groups of thehydrophilic polymer composition that is between about 1:1 and about 5:1,and can be between about 1.5:1 and about 3:1. For certain compositions,it is expected that this functional group parity of the hydrophobicpolymer composition to the hydrophilic polymer composition will resultin a topical composition precursor containing about 72 wt. % to about 98wt. % hydrophobic polymer composition and about 2 wt. % to about 25 wt.% hydrophilic polymer composition, based on the total weight of thetopical composition precursor.

A topical composition is provided according to the invention. Thetopical composition can include the topical composition precursor andcan include a result of diluting the topical composition precursor withwater. The topical composition preferably includes a result of hydratingthe topical composition precursor with water to provide at least about30 wt. % water. The topical composition can be characterized as aconcentrate if it contains between about 30 wt. % and about 70 wt. %water based on the weight of the topical composition. It is expectedthat the concentrate will be provided with a water concentration ofbetween about 30 wt. % and about 45 wt. % to reduce costs associatedwith shipping water. When the topical composition is provided as a usesolution for application to skin tissue, it is expected that thecomposition will contain at least about 70 wt. % water and can includebetween about 70 wt. % and about 96 wt. % water, based on the weight ofthe topical composition.

The topical composition can include active ingredients such asantimicrobials, antifungals, anti-inflammatory agents, anti-viralagents, drugs, sunscreens, vitamins, alpha-hydroxy acids, surfactants,dyes, fragrances and pigments.

The topical composition can include a surfactant or a mixture ofsurfactants to enhance the stability of the topical composition and/orto enhance the rate of release of active ingredients. Exemplarysurfactants that can be used according to the invention include nonionicsurfactants, anionic surfactants, cationic surfactants, amphotericsurfactants, and mixtures thereof. Exemplary nonionic surfactants thatcan be used according to the invention include ethoxylated surfactants,propoxylated surfactants, and ethoxylated-propoxylated surfactants. Anexemplary ethoxylated surfactant includes nonylphenol ethoxylate havingabout nine ethylene oxide repeating groups. The surfactant component canbe incorporated into the topical composition in an amount sufficient toprovide the desired stability and the desirable rate of release ofactive ingredients. In most applications, it is expected that thesurfactant will be provided in an amount of up to about 5 wt. %, andwill more likely be provided in an amount of between about 0.5 wt. % andabout 5 wt. %.

A method for manufacturing a topical composition is provided accordingto the invention. The method includes a step of melt processing amixture of a hydrophobic polymer composition and a hydrophilic polymercomposition to provide a topical composition precursor, and diluting thetopical composition precursor to provide a concentrate having a waterconcentration of at least about 30 wt. %, based on the weight of thetopical composition. The step of melt processing preferably includesmixing the hydrophobic polymer composition and the hydrophilic polymercomposition at a temperature of greater than 50° C., and more preferablygreater than about 125° C. The step of melt processing preferablyincludes mixing the hydrophobic polymer composition and the hydrophilicpolymer composition at a water concentration of less than about 1 wt. %.

A method for using a topical composition is provided according to theinvention. The method includes applying the topical composition to skintissue.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the change in percent free COOH of maleicacid/methylvinylether copolymer as a function of percentpolyvinylpyrrolidone with 1-eicosene;

FIG. 2 is a graph showing percent free COOH of MMVE as a function ofpercent PVPH added;

FIG. 3 is a graph of percent titratable COOH groups of MMVE as afunction of percent PVPE or PVPH added;

FIG. 4 is a graph showing the effects of adding 20 to 50 wt. % PVPE orPVPH on pKa and equivalent weight of MMVE;

FIG. 5 is a graph showing MMVE solution viscosity as a function ofpercent PVPH or percent PVPE added and temperature;

FIG. 6 is a graph showing MMVE viscosity as a function of temperatureand percent of PVPH and PVPE;

FIG. 7 is a graph showing the percent of polymer remaining bound tohydrophilic nylon membranes as a function of increasing percentage ofPVPH or PVPE polymer;

FIG. 8 is a graph showing the percent of polymer remaining bound tohydrophilic nylon membranes as a function of increasing percentage ofPVPH+5 wt. % or 10 wt. % PVPE polymer;

FIG. 9 is a graph showing the percent of starch-polymer complex bound asa function of percent PVPH at 5 wt. %, 10 wt. %, and 54 wt. % PVPE;

FIG. 10 is a graph showing the percent of PVOH-polymer complex bound asa function of percent PVPH at 5 wt. %, 10 wt. %, and 54 wt. % PVPE;

FIG. 11 is a graph showing the percent of CM-cellulose-polymer complexbound as a function of percent PVPH at 5 wt. %, 10 wt. %, and 54 wt. %PVPE;

FIG. 12 is a graph showing the percent of cyclodextrin PVPH and PVPEpolymer complex bound at 5 wt. %, 10 wt. %, and 54 wt. % PVPE;

FIG. 13 is a graph showing the percent of Dextran 70 polymer complexbound as a function of percent PVPH at 5 wt. %, 10 wt. %, and 54 wt. %PVPE;

FIG. 14 is a graph showing the pKa for MMVE/PVP polymer complex.

DETAILED DESCRIPTION OF THE INVENTION

A topical composition and a topical composition precursor are providedby the invention. The topical composition precursor refers to arelatively anhydrous composition that is used to form the topicalcomposition use solution or working solution. The topical compositionuse solution or working solution refers to the composition intended tobe applied directly to skin tissue. It should be understood that thephrase “topical composition” refers to any composition that includes thetopical composition precursor as a component or that can be formed fromthe topical composition precursor, and may be provided in the form of aprecursor, a concentrate, a use solution, or an intermediate in theproduction of a topical composition use solution.

The topical composition can be referred to as a delivery system when itincludes an active ingredient for delivery to skin tissue. The topicalcomposition according to the invention is advantageous because of itsability to bind or adhere to skin tissue for a length of time andbecause of its ability to hold or contain active ingredients within thecomposition to allow for delivery of the active ingredients to skintissue. It is expected that the topical composition is able to adhere orbind to skin tissue for at least about four hours and holds the activeingredients contained therein in proximity to skin tissue for thatlength of time to allow for delivery of the active ingredients to theskin tissue. In general, it is expected that the topical compositionwill bind or adhere to skin tissue for at least four hours even afterseveral applications of washing and scrubbing of the skin tissue. It isexpected that the natural exfoliation of the skin will cause the removalof most of the topical composition from the skin tissue.

The topical composition precursor can be prepared by melt processing ahydrophobic polymer composition and a hydrophilic polymer composition toprovide an interaction between the hydrophobic polymer composition andthe hydrophilic polymer composition. It should be understood that thephrase “melt processing” refers to mixing the hydrophobic polymercomposition and the hydrophilic polymer composition under conditionsthat provide that the hydrophobic polymer component of the hydrophobicpolymer composition and the hydrophilic polymer component of thehydrophilic polymer composition are in a liquid state so that theysufficiently mix. When the polymers are sufficiently mixed, it isbelieved that an interaction forms between the hydrophobic polymercomponent and the hydrophilic polymer component. The melt processingtemperature is preferably at least about 50° C. and more preferably atleast about 125° C. to generate this interaction.

It is believed the interaction exhibited between the hydrophobic polymercomponent and the hydrophilic polymer component is a type of complexformation reaction, and that the complexes, once formed, are stable inwater at temperatures up to 65° C. and at a pH range of 3.0 to 9.0. Bystable, it is meant that the complexes do not favor disassociation. Itis believed that this interaction provides the topical composition withan ability to bind or hold onto hydrophobic active ingredients that areemulsified in water, and provides the topical composition with anability to bind to skin and/or substrates of predominantly hydrophobiccharacter.

Hydrophobic Polymer Composition

The hydrophobic polymer composition that can be used according to theinvention includes repeating pyrrolidone/alkylene groups. Exemplarypolymers that have repeating pyrrolidone/alkylene groups includepoly(vinylpyrrolidone/alkylene) polymers.Poly(vinylpyrrolidone/alkylene) polymers include those polymers obtainedby a polymerizing alkylene substituted vinylpyrrolidone. The polymerscan be represented by the following general formula:

wherein R represents a carbon chain substitute such as an alkylene groupand n represents the number of repeating units. The R group ispreferably sufficiently long so that the polymer remains relativelywater insoluble and should not be too long so that the polymer isdifficult to melt process. Preferably, the alkylene group contains alength of at least about 10 carbon atoms and contains no more than about25 carbon atoms. Preferably, the alkylene group contains between about14 carbon atoms and about 22 carbon atoms, and more preferably betweenabout 15 carbon atoms and about 19 carbon atoms.

The poly(vinylpyrrolidone/alkylene) polymers that can be used accordingto the invention preferably have a molecular weight that is sufficientlyhigh so that the polymer maintains its water insolubility but themolecular weight should not be so high that it becomes difficult to meltprocess the polymer. Preferably, the weight average molecular weight ofthe poly(vinylpyrrolidone/alkylene) polymer is between about 3,000 andabout 400,000. Another way to characterize the size of thepoly(vinylpyrrolidone/alkylene) polymer is by the number of repeatingunits (n). In the case of a poly(vinylpyrrolidone/alkylene) polymerhaving a weight average molecular weight of between about 6,000 andabout 30,000, the poly(vinylpyrrolidone/alkylene) polymer has betweenabout 20 and about 80 repeating units, and more preferably between about30 and about 50 repeating units. It should be understood that repeatingunits refer to the residues of vinylpyrrolidone/alkylene groups.

Preferred poly(vinylpyrrolidone/alkylene) polymers that can be usedaccording to the invention include poly(vinylpyrrolidone/1-eicosene) andpoly(vinylpyrrolidone/hexadecene). Poly(vinylpyrrolidone/1-eicosene) canbe referred to as PVPE and is commonly used in pharmaceutical andcosmetic preparations. A preferred form of PVPE for use according to theinvention includes about 43 to 44 repeating units in length and has aweight average molecular weight of about 17,000 and can be characterizedas a paraffin-like solid. This particular PVPE is highly insoluble inwater, and has an extremely low oral toxicity (LD₅₀>17000 mg/kg) andexhibits no demonstrable dermal toxicity.Poly(vinylpyrrolidone/1-hexadecene) can be referred to as PVPH. Apreferred form of PVPH is available as a viscous yellow liquid that isinsoluble in water and has a low oral toxicity (LD₅₀>64000 mg/kg), hasabout 39 to 40 repeating units, a molecular weight of about 1,400, andexhibits no demonstrable dermal toxicity.

PVPE and PVPH differ in the length of the hydrocarbon side chain, andare used extensively in the skin care industry, usually inconcentrations of less than 1% by weight, because of their ability tobind to skin. Because the skin care industry generally prefers to applyactives to skin using a water-based composition, the use of PVPE andPVPH often requires solvents, surfactants, and emulsifiers to stabilizethese polymers in a water emulsion. However, many of the solvents,surfactants and emulsifiers used to stabilize PVPE and PVPH in a wateremulsion lack the low dermal toxicities of PVPE and PVPH. PVPE and PVPHby themselves lack a cosmetically elegant appeal when applied directlyto the skin. They tend to be sticky and greasy.

The hydrophobic polymer composition used according to the invention ispreferably provided as a mixture of differentpoly(vinylpyrrolidone/alkylene) polymers. The mixtures of differentpoly(vinylpyrrolidone/alkylene) polymers preferably include at least 5wt. % of a first poly(vinylpyrrolidone/alkylene) polymer based on theweight of the hydrophobic polymer composition. The hydrophobic polymercomposition preferably includes between about 5 wt. % and about 54 wt. %of the first poly(vinylpyrrolidone/alkylene) polymer. The secondpoly(vinylpyrrolidone/alkylene) polymer is preferably provided in anamount of at least about 46 wt. % and preferably in a range of betweenabout 46 wt. % and 95 wt. %. For a hydrophobic polymer compositioncontaining a first poly(vinylpyrrolidone/alkylene) polymer and a secondpoly(vinylpyrrolidone/alkylene) polymer, the mole ratio of the firstpolymer to the second polymer is preferably between about 1:22 and about1:1. In general, when the hydrophobic polymer composition contains amixture of different poly(vinylpyrrolidone/alkylene) polymers, it ispreferable to provide at least one of thepoly(vinylpyrrolidone/alkylene) polymers in an amount that providesimproved properties to the topical composition compared to a topicalcomposition having a hydrophobic polymer composition containing a singlepoly(vinylpyrrolidone/alkylene) polymer.

When the hydrophobic polymer composition is provided as a mixture ofPVPH and PVPE, it is preferable that the PVPH is provided in the rangeof between about 46 wt. % to about 95 wt. % and the PVPE is provided inthe range of between about 5 wt. % and about 65 wt. %, based upon theweight of the hydrophobic polymer composition.

Hydrophilic Polymer Composition The hydrophilic polymer composition thatcan be used according to the invention includes at least one hydrophilicpolymer and may include a mixture of hydrophilic polymers. Thehydrophilic polymers that can be used according to the invention includepolymers having repeating carboxylic acid groups and/or hydroxyl groups.Preferred hydrophilic polymers that can be used according to theinvention include polyacrylic acid polymers and poly(maleicacid/methylvinylether) copolymers.

Polyacrylic acid polymers that can be used according to the inventionpreferably have a weight average molecular weight of at least about50,000, and more preferably between about 50,000 and about 4,000,000. Inaddition, the polyacrylic acid polymers preferably have a level ofcross-linking that is less than about 1%. A general structuralrepresentation of polyacrylic acid polymers is shown below:

wherein n is the number of repeating units and is preferably betweenabout 1,000 and about 20,000.

Poly(maleic acid/methylvinylether) copolymers that can be used accordingto the invention preferably have a weight average molecular weight of atleast about 50,000, and preferably between about 50,000 and about4,000,000. The weight average molecular weight is more preferablybetween about 70,000 and 2,500,000. A general structural representationof poly(maleic acid/methylvinylether) copolymers is shown below:

wherein n is the number of repeating units and is preferably betweenabout 200 and about 20,000.

Additional hydrophilic polymers that can be used according to theinvention include starch, derivatives of starch, polyvinyl alcohol,cellulose, derivatives of cellulose, carboxymethyl cellulose,cyclodextrins, and dextrans. Exemplary starches include amylopectin andpolyglucose. The weight average molecular weight of the hydrophilicpolymers is preferably sufficient to provide solubility in water but nottoo high to become difficult to process. Starches that can be usedaccording to the invention preferably have a weight average molecularweight of between about 50,000 and about 20,000,000. A derivative ofstarch that can be used according to the invention includes partiallyhydrolized starch. Cellulose that can be used according to the inventionpreferably has a weight average molecular weight of between about 50,000and about 15,000,000. Polyglucose that can be used according to theinvention can be characterized as low fraction polyglucose having aweight average molecular weight of between about 60,000 and about90,000, and high fraction polyglucose having a weight average molecularweight of between about 90,000 and about 300,000. An exemplary lowfraction polyglucose material that can be used according to theinvention is available under the name Dextran-70. In general, this typeof polyglucose has all alpha 1-6 linkages. Starch derivatives that canbe used according to the invention include those starch derivativeshaving alpha 1-4 linkages. An example of this type of starch derivativeincludes cyclodextrins. Preferred cyclodextrins that can be usedaccording to the invention are those that act to provide a cavity withinthe molecule large enough to contain components desirable for topicalapplications. Preferably, the cyclodextrins that can be used accordingto the invention have a molecular weight of between about 900 and about1,400. Polyvinyl alcohols that can be used according to the inventionpreferably have a weight average molecular weight of between about50,000 and about 200,000.

Exemplary hydrophilic polymers that can be used according to theinvention include those polymers having the following meltingtemperature range and the following maximum temperature range beyondwhich it is expected decomposition of the polymer will occur. Exemplarypoly(maleic acid/methylvinylether) copolymers that can be used includethose having a melting temperature range of between about 60° C. andabout 65° C. and a maximum temperature range of between about 80° C. andabout 90° C. Exemplary polyacrylic acid polymers that can be usedinclude those having a melting temperature range of between about 65° C.and about 70° C. and a maximum temperature range of between about 80° C.and about 90° C. Exemplary carboxymethyl cellulose polymers that can beused include those having a melting temperature range of between about55° C. and about 60° C. and a maximum temperature range of between about75° C. and about 80° C. Exemplary polyvinyl alcohol polymers that can beused include those having a melting temperature range of between about50° C. and about 55° C. and a maximum temperature range of between about65° C. and about 70° C. Exemplary starches that can be used includethose having a melting temperature range of between about 40° C. andabout 45° C. and a maximum temperature range of between about 50° C. andabout 55° C. Exemplary dextrans that can be used include those having amelting temperature range of between about 37° C. and about 40° C. and amaximum temperature range of between about 45° C. and about 50° C.Exemplary β-cyclodextrins that can be used according to the inventioninclude those having a melting temperature range of between about 40° C.and about 45° C. and a maximum temperature range of between about 65° C.and about 70° C.

Processing

The hydrophobic polymer composition and the hydrophilic polymercomposition are preferably combined and heated to at least about 50° C.to provide a polymer melt. The composition is preferably heated to atleast about 125° C. under mixing to form complexes between thehydrophobic and hydrophilic polymers.

The complex formation step is preferably carried out in a relativelyanhydrous environment. That is, the amount of water provided in thecomposition during the complex formation step is preferably less thanabout 1 wt. %. Once the desired level of complex formation has occurred,the composition can be hydrated with water.

The hydrophobic polymer composition and the hydrophilic polymercomposition are preferably mixed together in amounts sufficient toprovide a ratio of pyrrolidone groups to the combination of carboxylicacid groups and hydroxyl groups of between about 1:1 and about 5:1. Theratio of the structures causing the observed interaction between thehydrophobic polymer composition and the hydrophilic polymer compositioncan be referred to as “functional group parity.” Preferably, the ratioof pyrrolidone groups to the combination of carboxylic acid groups andhydroxyl groups is between about 1.5:1 and about 3:1. In order to drivethe complex formation reaction, it is desirable to provide an imbalancebetween the two types of groups. Accordingly, it is generally desirableto provide more of the pyrrolidone groups than the combination ofcarboxylic groups and the hydroxyl groups. It should be understood thatthe reference to a “combination of carboxylic groups and hydroxylgroups” refers to the total amount of carboxylic groups and hydroxylgroups present but does not require the presence of both carboxylicgroups and hydroxyl groups. For example, the value of the combination ofcarboxylic groups and hydroxyl groups can be determined for acomposition that contains only carboxylic groups. Similarly, the valuecan be determined for a composition that contains only hydroxyl groups.

During the complex formation step, the amounts of hydrophobic polymercomposition and hydrophilic polymer composition can be characterized ona weight percent basis. Preferably, about 2 wt. % to about 28 wt. %hydrophilic polymer composition and about 72 wt. % to about 98 wt. %hydrophobic polymer composition are combined to provide for complexformation. Preferably, about 8 wt. % to about 25 wt. % hydrophilicpolymer composition and about 72 wt. % to about 95 wt. % hydrophobicpolymer composition are combined to form the complex. During the complexformation step, the amount of water available in the composition ispreferably less than about 1 wt. %. Although the complex formingcomposition can be relatively anhydrous, it is expected that the amountof water will be between about 0.3 wt. % and about 1.0 wt. %.

Once the hydrophobic polymers and the hydrophilic polymers havesufficiently reacted or interacted to form complexes, it is desirable toadd water to the composition to provide a stable aqueous compositionthat can be relatively easily further hydrated. The stable aqueouscomposition that can be easily diluted further with water to form theuse solution can be referred to as the concentrate. It is generallydesirable to hydrate the composition to a water content that provides arelatively stable composition and that allows for water to be added at alater date without much difficulty. Although water can be added to thecomposition to a level equivalent to the level of the topicalcomposition use solution, it is desirable to minimize the amount ofwater to avoid having to ship water. Shipping excess water is expectedto add cost to the composition. In addition, it has been found that thefirst hydration of the topical composition precursor is the mostdifficult hydration step because of the need to control the conditionsof hydration. After the first hydration to a water content of at leastabout 30 wt. %, it is expected that further hydrations to higher watercontents are relatively easy and can be accomplished by simply mixingthe composition with water. Accordingly, the amount of water provided inthe composition when made available as a concentrate for shipment ispreferably between about 30 wt. % and about 45 wt. %. When thecomposition includes about 30 wt. % to about 45 wt. % water, it isexpected that the composition will include between about 3 wt. % andabout 10 wt. % hydrophilic polymer composition and between about 30 wt.% and about 50 wt. % hydrophobic polymer composition.

Water is added to the relatively anhydrous composition by mixing waterand the relatively anhydrous composition at a temperature and for a timesufficient to allow the composition to become hydrated without losingsignificant amounts of interaction between the hydrophobic polymercomposition and the hydrophilic polymer composition. In general, therelatively anhydrous composition is hydrated by heating to at least 60°C. and adding water while mixing. Preferably, the composition is heatedto at least about 65° C. and more preferably at least about 70° C. Apreferred temperature range is about 65° C. to about 80° C.

The relatively anhydrous composition can be referred to as the topicalcomposition precursor. The topical composition having a waterconcentration of between about 30 wt. % and about 95 wt. % can bereferred to as the concentrate. It is expected that the concentrate willbe made available to manufacturers of topical compositions. In addition,it is expected that the concentrate made available to manufacturers oftopical compositions will have a water concentration of between about 30wt. % and about 45 wt. %. The manufacturers of topical compositions willeither further hydrate the composition or use it as it is made availableto them. In most applications, it is expected that the topicalcomposition manufacturers will dilute the topical compositionconcentrate to the desired concentration of water and polymercomponents, and then use that composition as a component of the topicalcomposition.

Additional Components

The topical composition use solution is preferably prepared by mixingthe topical composition concentrate with additional components for theformation of the use solution. Components that can be incorporated intothe composition for forming the use solution include those componentsnormally encountered in the topical composition industry. Exemplarycomponents include antimicrobial agents, antifungal agents,anti-inflammatory agents, anti-viral agents, sunscreens, vitamins,α-hydroxy acids, surfactants, pigments, and dyes. Components that aregenerally best suited for the composition of the invention include thoseactive ingredients that can be characterized as hydrophobic, neutralpolar such as alcohols, and acidic.

Exemplary antimicrobial agents or biocidal agents that can be usedaccording to the invention include those agents that are known to thoseof skill in the art, including quaternary ammonium compounds andperoxygen compounds such as peroxy acids. Biocidal agents that can beused include chlorinated diphenyl ethers such as those available underthe tradename Triclosan®. When used, this agent can be present at aconcentration of about 0.9 to about 1.1 wt-%, more preferably about 1.0wt-%. Tricosan® gives a broad spectrum of pathogenic coverage and has along history of safe usage with a benign toxicological profile. Anexemplary natural antimicrobial agent that can be used for treatinginflammation and psoriasis includes silver.

Exemplary antifungal agents that can be used include sulconazole,naftifine, morpholines, allylamines, triazoles, clotrimazole andmiconazole nitrate.

The topical composition can also be used as long lasting carriers forinsecticides. A number of insecticides are known in the art as safe forhuman use, including citronella. Preferred insecticides includeN,N′-diethyl-3-methylbenzamide, commonly known as DEET.

Exemplary sunscreen agents that can be used include FSDA approvedmaterials such as aminobenzoic acid-PABA, cinoxate, diethanolaminemethoxycinnamate, digalloyl trioleate, dioxybenzone, ethyl4[bis(hydroxypropyl)] aminobenzoate, glyceryl aminobenzoate, homosalate,lawsone with dihydroxyacetone, mentyl anthranilate, octocrylene, octylmethoxycinnamate, octyl salicylate, oxybenzone, benzophenone, padimate,phenylbenzimidazole sulfonic acid, red petrolaum, sulisobenzone,titanium dioxide, trolamine salicylate, and combinations of the above.Preferred sunscreen materials include a mixture of octylmethoxycinnamate and benzophenone.

Exemplary active ingredients that can be used in the topical compositioninclude benzalkonium chloride (antimicrobial), benzophenone (sunscreen),glycerin (skin moisturizer), iodine (antimicrobial), vitamin A (skinhealing), vitamin D and D2 (skin healing), aloe (skin healing), octylmethoxycinnamate (sunscreen), anise oil, garlic oil, hydrocortisone(anti-inflammatory), salicylic acid (acne preparation), DEET (insectrepellent), phenol-TEA complex (antimicrobial), clotrimazole(antifungal), and miconazole nitrate (antifungal).

Active ingredients that can be used in the topical composition accordingto the invention include natural and synthetic drugs. Exemplary drugsthat can be used for topical applications include those listed in U.S.Pharmacopeia and National Formulary, The United States PharmacopeialConvention, Inc., Rockville, Md. and Physician's Desk Reference, MedicalEconomics Co., Inc., Oradell, N.J.

Surfactants can be incorporated into the topical composition to providecontrolled release of active ingredient or other component in thetopical composition. It is expected that the amount of surfactant andthe type of surfactant can be adjusted to increase or decrease therelease rate. In the case where an active ingredient or other componentdesired to be released is relatively more hydrophobic, it is expectedthat by increasing the surfactant concentration, an equilibrium shiftfavors the aqueous phase and promotes a faster release of theingredient.

Surfactants that can be incorporated into the topical compositionaccording to the invention include nonionic surfactants, cationicsurfactants, anionic surfactants, and amphoteric surfactants, andmixtures thereof. It may be desirable to use surfactants when they havea tendency to increase the emulsion stability and/or to promote therelease of active ingredients. That is, surfactants can be used toincrease the water solubility of the polymers of the topical compositionand/or the surfactants can be used to decrease the binding of the activeingredients to the polymers of the topical composition.

Nonionic surfactants that can be used according to the invention includeethoxylated, propoxylated, ethoxylated-propoxylated surfactants, andmixtures thereof. An exemplary nonionic surfactant that can be useaccording to the invention includes nonylphenol ethoxylate having nineethylene oxide groups and is available under the name Nonoxynol-9. Whennonylphenol ethoxylate is used according to the invention, it ispreferably provided in an amount of up to 5 wt. %, and can be providedat a concentration of between about 0.5 wt. % and about 5 wt. %, and ata concentration of between about 0.6 wt. % and about 1 wt. %. Asdiscussed previously, the amount of the surfactant can be adjusted toprovide desired emulsion stability and to effect the rate of release ofactive ingredient.

The use of surfactants for releasing active ingredients from the topicalcomposition is believed to be most useful with active ingredients thatcan be characterized as hydrophobic.

Anionic surfactants that can be used according to the invention includessalts of carboxylic (soaps) and sulfonate salts (detergents). Cationicsurfactants that can be used according to the invention include amidessuch as cocoamide. One concern with the use of anionic surfactants,cationic surfactants, and amphoteric surfactants relates to thepotential destabilization of a emulsions as a result of the presence ofsalts. Accordingly, it may be desirable to use anionic surfactants,cationic surfactants, and amphoteric surfactants at sufficiently lowlevels to reduce this destabilizing effect. It is expected that thesesurfactants will be used at lower levels than nonionic surfactants. Inaddition, the positive charge of the cationic surfactants and theamphoteric surfactants can have an affect of forming insoluablecomplexes with portions of the hydrophilic polymer composition.

When surfactants are used according to the invention, it is generallydesirable to use the surfactant or mixture of surfactants in an amountthat provides a desired level of emulsion stability and provides adesired rate of release of active ingredients. It is expected that inmost applications, the surfactant or mixture of surfactants will beprovided at a concentration of up to about 5 wt. %, and can be providedin a range of 0.5 wt. % and 5 wt. %, and within a narrower range ofabout 0.6 wt. % and about 1 wt. %.

Although the topical composition has been described as a compositionthat includes additional components, it should be understood that thetopical composition can be used as a replacement for chemicals oradditives used in presently available topical compositions that are onthe market. That is, certain ingredients of existing topicalcompositions can be replaced by the topical composition of theinvention. For example, may commercially available topical compositionsinclude several chemicals such as solvents or surfactants that are usedto hold active ingredients in the composition. The topical compositionof the invention can be used to hold or solubilize active ingredientswithout the use of the solvents or other components required by certaincommercially available topical compositions.

The topical composition use solution according to the invention can beprovided in numerous applications. The composition can be provided as askin care product which is often used to administer vitamins, aloe,herbs, and drugs to skin tissue. Exemplary vitamins that are oftendelivered include vitamin A, vitamin E, and retinoic acid. Additionally,essential fatty acids such as borage oil and herbs such as aloe vera andevening primrose can be incorporated into the composition.

The topical composition can be used as a cosmetic composition. Exemplarycosmetic compositions according to the invention include lip careproducts such as lipstick and lip gloss, eye care products, skin careproducts, fragrances, botanicals, oils, herbs, baby products, bathproducts, soaps, pigments, scents, alcohols, flavors, aloe, glycerin,powders, nail polish, and foundation.

The topical composition can be used as a barrier composition to providea barrier layer between skin tissue and the external environment.

The composition according to the invention can be provided as over thecounter products or prescription products. Exemplary over the counterproducts include sunscreens, sun blocks, insect repellants, wound careproducts, burn care products, sunless tanning products, antifungalproducts, antibacterial products, antiviral products, acne preventionproducts, bath products, vitamins, minerals, deodorants, andanti-perspirants. The over the counter products can include drugs and/orpharmaceuticals. Prescription products can include peptides, metals,and/or drugs for skin disorders.

The composition according to the invention can be used as a hair careproduct, an animal care products, and a home care product. Exemplaryhair care products according to the invention include shampoos,conditioners, mousses, stylers, finishers, dyes, and hair sprays.Exemplary animal care products include soaps, hair shampoo, hairconditioners, flea and tick baths, and prescription drugs for skindiseases. Exemplary home care products include towelettes,disinfectants, soaps, and cleaners.

The composition according to the invention can be used to provide anautocare product. Exemplary autocare products according to the inventioninclude fabrics, leathers, vinyls, paints, metals, chromes, rubber,tires, and window treatments.

EXAMPLES

The following examples were carried out in order to demonstrate certainteachings of the invention. It should be understood that the inventionis not limited to the examples of this application.

Example 1

Polyacrylic acid having less than 1% cross linking with a weight averagemolecular weight of between 400,000 and 500,000 and maleicacid/methylvinylether copolymer(MMVE) with a weight average molecularweight of 1,980,000 were used. For simplicity and ease of handling dueto lower solution viscosities, the majority of work was performed usingMMVE. The acidic polymers were easier to study by simple pH titrationsof free —COOH groups. When increasing concentrations of PVPE up to 10%were mixed with MMVE or PA under anhydrous conditions at temperatures of75° C. to 125° C., translucent, amber, waxy solids or liquids of highviscosity resulted. When heated in water to 65° C. and polymerconcentrations of 10-15% suspensions were obtained that could then betitrated with normal KOH. Results are shown in FIG. 1. Mixtures of MMVEand PVPH prepared in the same way gave the results shown in FIG. 2.

FIGS. 1 and 2 show MMVE without any added PVPE or PVPH has only 50% ofthe —COOH groups titratable by KOH. Many Organic Chemistry textbooks usethe following structure to describe the hydrogen bonding interactions ofcarboxylic acids.

For low formula weight carboxylic acids, the hydrogen bondinginteractions are considered weak ones in the area of 5 kcal/mole. Withpolymers having hundreds of —COOH groups per molecule and the addedcomplexity of inter-chain as well as intra-chain interactions, thesetypes of structures are likely quite stable and would require largeenergy input to disrupt them. Steric factors likely contributeadditional stabilizing factors.

FIGS. 1 and 2 also show that MMVE hydrogen bond structure is extensivelydisrupted by the addition of as little as 1% PVPE or PVPH. Adding morePVPE or PVPH results in the disappearance of —COOH groups. As seen inFIG. 3, the disappearance of —COOH groups is linear to slightlysinusoidal between 2 and 10% PVPE or PVPH.

FIG. 4 shows the effects on MMVE titration curves with the addition of20-50% PVPE or PVPH. The intention here is to maximize skin binding(hydrophobic character) without extensive loss of water solubility(hydrophilic character).

In the legend to FIG. 4 “HP” refers to “Hydrophobic Polymers” as thedata applies to PVPE and PVPH equally. FIG. 4 shows that while the “pKa”of MMVE changes slightly from 5 to 5.36, the mEqs. of Normal KOHrequired to reach the pKa is reduced by 75%, meaning that the number oftitratable —COOH groups also has been reduced and the Equivalent Weightof MMVE has increased. Clearly there is an interaction between the —COOHgroups of MMVE and PVPE and/or PVPH. It is difficult to perceive thisinteraction occurring between the C₁₆ and/or C₂₀ aliphatic side-chainsof PVPH and PVPE. We believe the pyrrolidone ring shown below isresponsible for this interaction.

This is the structure of N-methylpyrrolidone, which has the samecovalent structure as the pyrrolidone rings in PVPE and PVPH. Thepyrrolidone ring is chemically very stable, yet it has a carbonyl oxygenthat is electronegative and the amide nitrogen has a free pair ofelectrons, which can participate in resonance.

We believe the following structure explains the simplest form of anon-covalent complex between PA or MMVE and PVPE and/or PVPH.

We realize that this complex as presented here is a simplistic form andmay not exist at all primarily from steric considerations. The complexmay not involve adjacent —COOH groups or pyrrolidone rings. The actualcomplex most likely involves intra-chain and inter-chain interactions,resulting in a three dimensional structure far too complex to present.

Example 2

Another tool for studying polymers is viscosity. We hoped to learn moreinformation about the complexes by looking at viscosity measurements atvariable concentrations of PVPE and PVPH and also as a function oftemperature. FIG. 5 shows the results of these studies at a polymerconcentration of 100 mg/ml. in water, and PVPE or PVPH concentrations of0 to 10% at a pH of 8.0, and over the temperature range of 32° C. to 65°C.

The surfaces of these plots are remarkably similar with a fewexceptions. At 2%, PVPE (blue surface) increases while PVPH (yellowsurface) decreases. This decrease in viscosity recurs between 6% and 10%concentrations, and persists up to 50° C. Attempts were made to extendthe study to lower total polymer concentrations (<100 mg/ml). Thisresulted in the complex dissociating at ˜10 mg/ml and completelycollapsing to starting materials at 5 mg/ml. PVPH was more prone to thisdissociation than PVPE.

Since complex formation appears essentially the same with either PVPH orPVPE, we decided to look at complexes formed with a mixture of PVPH andPVPE. A molar ratio of 1:1 was chosen to begin the studies. Viscositydata for this mixture is shown in FIG. 6.

Comparison of FIG. 5 with FIG. 6 shows that the drop in viscosity from6-10% concentration of PVPH+PVPE is greater than with PVPH alone, andthe slope of the surface as a function of temperature is less with thePVPH+PVPE mixture than with either PVPH or PVPE alone. This interactionbetween PVPH and PVPE was unexpected.

It is believed that two types of phase separations occur with thepolymer complexes. The first is an upper phase of opaque, whitematerial. This is the result of insolubility of the complex. The secondis an upper layer of clear oily droplets or a waxy solid. This is theresult of complex decomposition.

Example 3

Since the polymer composition according to the invention is designed tobind to the skin with resistance to wash-off, we developed a simple andrapid, gravimetric method to mimic skin application of the polymersystem. This test utilizes hydrophilic nylon membranes normally used forsolvent filtration. It is expected that these membranes possess mixedhydrophilic and hydrophobic properties similar to skin.

The membranes are weighed to the nearest 0.1 mg. The pre-weighedmembranes are floated on a suspension of the test polymer solution andweighed to obtain the wet weight of sample applied. The membranes withtest polymer are dried at 32-35° C. (skin temperature) for 30 minutes,and a dry weight is obtained. The dried membranes may then be soaked inwater or a variety of solvents, re-dried and weighed a final time toyield the mg or % of polymer remaining on the membrane after treatment.It is expected that results on skin will be better.

FIG. 7 shows the results of our binding study with MMVE complexes ofPVPH, PVPE and a 1:1 molar ratio of PVPH+PVPE.

Error bars indicate standard deviation of the mean. The expected resultswere that PVPE+PVPH>=PVPE>PVPH, reasoning that the C₂₀ side chain ofPVPE should adhere better than the shorter C₁₆ side chain of PVPH.However, the data clearly show that the complex of MMVE: PVPE is muchmore soluble in water than the complexes of MMVE: PVPH or MMVE:PVPH+PVPE. The high binding point at 10% PVPH is also tantalizing,however, complexes containing 10% hydrophobic polymer or less decomposeto two phases in water within 24 hours of preparation. The MMVE:PVPH+PVPE curve hints that a cooperative interaction between PVPH andPVPE may be beneficial, but at lower molar ratios than 1:1. Similarstudies were conducted with PVPH: PVPE ratios of 10:1 and 22:1. Thesedata are shown in FIG. 8.

FIG. 8 clearly shows the synergism between PVPE and PVPH. Either PVPH:PVPE mixture 10:1 M (10%) or the 22:1 M (5%) result in 15-25% greaterbinding to the membranes than seen by either hydrophobic polymer aloneor the 1:1 M ratio of the two. FIG. 8 also shows that a mixture of 95%PVPH+5% PVPE and 50% MMVE-H₂O yields a product that 75% remains bound tothe membranes after two hours of immersion in water. Similar bindingdata demonstrated the PA−PVPE+PVPH system was substantially the same(data not shown). At this point we considered the acidic hydrophilic andPVPE+PVPH system optimized.

Implied by the non-covalent structure is an equilibrium process forcomplex formation. The reversible nature of the complex by dilution alsoimplies an equilibrium complex. Calculation of the ratio of pyrrolidonegroups of PVPH+PVPE to —COOH groups of MMVE for the optimized, hydratedcomplex described above gives a value of 2.29:1. Because of the natureof the proposed complex, this value seems low. Complicating the issue isthe fact that the complexes form emulsions, implying the complexes arenot truly in solution, but are merely a suspension of micelles. Thisline of reasoning leads to the conclusion that the factors controllingthe equilibrium (or rather equilibria, there are likely many) are notprimarily involved with the aqueous phase. This conclusion accounts forthe high stability of what may be thought of as a labile complex.

The MMVE and PA polymer complexes described to this point require theneutralization of —COOH groups for water solubility. This necessarilylimits the useful pH range to 6-9 for formulation. It is expected thatsimilar complexes should also form with hydrophilic polymers containing—OH groups instead of —COOH groups.

There are thousands of naturally occurring and man-made polymers withabundant —OH groups. Among these are starch, cellulose, derivatives ofstarch, derivatives of cellulose, carboxymethyl cellulose, polyvinylalcohol, cyclodextrins, and dextrans. There is also the possibility thatpolyvinylpyrrolidone (Povidone) may also interact with PVPH+PVPE.

All of the above compounds formed complexes with PVPE: PVPH mixturesunder anhydrous conditions at temperatures between 80-110° C. Thecomplexes were clear to translucent amber solids or high viscosityliquids. Hydration of these complexes to a total of 40-46% water at 65°C., produced hard, white to off-white, granular or waxy solids. Furtherdilution to working solutions of 10-15% polymer required the addition of0.5-10% surfactant (most often 9 to 10 mole nonylphenolethoxylates) toachieve stable emulsions.

In an attempt to overcome the difficulty of forming stable, aqueousemulsions, we dissolved the hydrophilic polymers in water atconcentrations of 11-17%, depending on the polymer's solubility thenadded PVPE: PVPH mixtures to final concentrations of 46-51% and heatedto 80-95° C. These reactions produced materials indistinguishable fromthe products formed under anhydrous conditions and hydratedpost-synthesis.

As the —OH group polymers offer no easily analyzable groups as we hadwith MMVE and PA polymers above, we began looking at binding data. Theresults for starch are shown in FIG. 9.

Unlike the MMVE polymer complex, 5 or 10% PVPE showed very littledifference in binding. Binding appears maximized at 10-20% PVPH+5 or 10%PVPE.

However, significant decomposition (see Note above) of the complexoccurred at 10 and 20% PVPH+5 or 10% PVPE. The lowest stableconcentration was 30% PVPH+PVPE at all levels of PVPE, and the moststable aqueous emulsion paradoxically was at 40% PVPH+54% PVPE (1:1 M).

Results with polymer complexes utilizing polyvinylalcohol (PVOH) as thehydrophilic portion are shown in FIG. 10.

Carboxymethylcellulose (CMC), like PA mentioned above, is commerciallyused as a viscosity builder for aqueous solutions. A 1% solution of CMChas a viscosity of ˜2,000 Csts/s. A 1% solution of PA at neutral pH hasa viscosity of >4,000 Csts/s. At acidic pH, a 1% solution of PA has aviscosity of ˜250 Csts/s. Neutralization of the —COOH groups on PAcauses the increase in viscosity. CMC requires no such neutralization asthe —COOH groups are tied up as methyl esters.

Complex formation of CMC and PA with PVPH+PVPE mixtures givesdrastically different results. Complexes of PA under anhydrousconditions at 90 to 125° C. and subsequent hydration to a 40% watercontent, yields solutions or gels of extremely high viscosity, as if the—COOH groups have been neutralized, or are unavailable for titration asseen with MMVE. Subsequent dilution of these gels to 0.68% PA content,results in solutions of ˜5500 Csts/s. This is a considerable increase inviscosity over PA alone.

Complex formation with CMC under similar conditions results in asubstantial decrease in solution viscosity. PVPH+PVPE content in excessof 30% and dilution to a 1% concentration of CMC gives a solutionviscosity of ˜800 Csts/s.

Although the complexes formed with CMC and PA are believed to be similaras shown in FIGS. 11 and 17, the results of the complex formation havedrastically different effects on CMC and PA ability to increase solutionviscosity.

Results of the membrane binding studies with the CMC PVPH+PVPE complexesare shown in FIG. 11.

FIG. 11 shows that the CMC-PVPH+54% PVPE yields a higher degree ofbinding at all concentrations of PVPH+PVPE. At 40% PVPE+PVPH the 10%PVPE mixture is equivalent to the 54% PVPE mixture.

Cyclodextrins offer an interesting opportunity. Cyclodextrins are usedas encapsulants in the food, cosmetic and pharmaceutical industry. Theyare cyclic oligosaccharides having 5 to 8 sugar residues with cavitiesin their centers. These cavities accommodate a wide variety of “guest”molecules that form stable complexes. The “guest” molecules may then bereleased under controlled conditions. Formation of guest complexes canalso stabilize molecules that are volatile or decompose in water. Apreferred cyclodextrin that can be used according to the invention isβ-cyclodextrin having seven glucose residues and has a central cavity6.5 Å in diameter and a formula weight of 1135. A representation of thismaterial is provided below.

Each glucose residue has 3 —OH groups (similar to Starch and CMC) thatoffer an opportunity for complex formation with PVPH+PVPE. It isdesirable to produce a polymer complex that is capable of encapsulatinga variety of active agents that will also bind tightly to hydrophobicsubstrates such as skin. Cyclodextrins are too water soluble to bind tothe skin for any appreciable time, particularly if the skin issubsequently exposed to water.

Most of the complexes with PVPH+PVPE shown in FIG. 12 lack anyappreciable solubility in water, a property that has been characteristicof all other polymer complexes. The notable exceptions are 10 and 20%PVPH+54% PVPE, which are completely soluble in water (pyrrolidone:—OHratios of 0.4 and 0.8 respectively). Since the cavity in theβ-cyclodextrin is known to be hydrophobic, and the water solubility ofthe guest effects the water solubility of the cyclodextrin complex, itis possible that PVPH and/or PVPE have occupied the cavity as a Guestmolecule. In addition, β-cyclodextrin is a relatively small moleculewith all of its —OH groups lying on the outside of the molecule. If allof the —OH groups formed complexes with pyrrolidone groups, none wouldbe available to promote water solubility. All of the complexes shown inFIG. 12, with the exceptions noted above, are soluble in nonpolarsolvents. This accounts for the >90% binding of the majority ofcomplexes in FIG. 12.

Closely related are the dextrans. Dextran is an oligosaccharide ofglucose residues held together with α-1,6 glycosidic linkages much likestarch. Dextrans lack the α-1,4 glycosidic linkages seen in amylopectin.Each glucose residue contains 3 —OH groups to complex with PVPH+PVPE.Dextrans are used commercially as fillers, thickeners and wettingagents. A preferred dextran according to the invention is Dextran-70having a weight average molecular weight of 70,000 and a range of60-90,000 (Low Fraction).

Dextran-70 is extremely soluble in water. It was anticipated that highlevels of PVPH+PVPE would be required to achieve the water resistantbinding we desired. This was not the case as seen in FIG. 13. Bindingrose sharply from 3% for the Dextran alone to nearly 80% with theaddition of 10% PVPH+PVPE. Binding remained nearly constant over therange of PVPH+PVPE concentrations. All of the complexes formed stableemulsions.

Polyvinylpyrrolidone (PVP) forms sticky, yellow complexes with bothPVPH+PVPE mixtures and hydrophilic polymers. Although quite watersoluble itself, most of the complexes formed with PVP are highlyinsoluble in water. The complex formed between MMVE and PVP is a hard,transparent solid. This complex is soluble in water at a pH of 4.0 orhigher. FIG. 14 shows the titration curve for MMVE/PVP produced atfunctional group parity ratio of 0.9 —COOH/pyrrolidone.

When FIG. 14 is compared to the native MMVE data presented in FIG. 4,calculation of the Equivalent Weight of MMVE is 168, which is nearlytwice the expected value of 87, based on the composition of MMVE. Thiscalculation indicates ˜51% of the —COOH groups on MMVE are not availablefor titration. Calculation of the Equivalent Weight of the MMVE/PVPcomplex in FIG. 14, gives a value of 448, indicating ˜19% of the —COOHare available for titration. Since PVP has no aliphatic side chains, the—COOH groups of MMVE must be tied up in a complex with the pyrrolidonerings as proposed in FIG. 11.

PVP is unique in our polymer complex system in that it can besubstituted for either the hydrophobic polymers or the hydrophilicpolymers and yet forms the same types of complexes. Complexes withPVPH+PVPE are soluble only in nonpolar solvents.

The PVP-PVPH+PVPE complex is soluble in ether-alcohol 75:25 or hexane.The PVP-CMC complex, formed in aqueous solution, retains extremely highviscosity and limited water solubility, requiring hydration levels inexcess of 85% to obtain working viscosities. PVP-CMC dries to a hard,transparent, brittle film. Once dried, the film is difficult to hydrate.

The above specification, examples and data provide a completedescription of the manufacture and use of the composition of theinvention. Since many embodiments of the invention can be made withoutdeparting from the spirit and scope of the invention, the inventionresides in the claims hereinafter appended.

What is claimed is:
 1. A method for manufacturing a topical composition,the method comprising steps of: (a) melt processing a mixture to providea topical composition precursor, the mixture comprising: (i) hydrophobicpolymer composition comprising repeating pyrrolidone/alkylene groups,wherein the alkylene groups contain at least 10 carbon atoms; (ii)hydrophilic polymer composition comprising repeating carboxylic acidgroups and/or repeating hydroxyl groups; and (iii) less than about 1 wt.% water; and (b) diluting the topical composition precursor to provide awater concentration of at least about 30 wt. % based on the weight ofthe topical composition.
 2. A method according to claim 1, furthercomprising a step of: (a) adding at least one active ingredient to thetopical composition, the active ingredient comprising at least one ofantimicrobial agent, antifungal agent, anti-inflammatory agent,anti-viral agent, drugs, sunscreens, vitamins, α-hydroxy acids,surfactants, fragrances, pigments, and dyes.
 3. A method according toclaim 1, wherein the step of melt processing comprises mixing thehydrophobic polymer composition and the hydrophilic polymer compositionat a temperature of greater than 50° C.
 4. A method according to claim1, wherein the step of melt processing comprises mixing the hydrophobicpolymer composition and the hydrophilic polymer composition at atemperature of greater than 125° C.
 5. A method according to claim 1,further comprising a step of: (a) diluting the topical compositionprecursor with water to provide a composition containing between about30 wt. % and about 45 wt. % water based on the weight of the topicalcomposition.
 6. A method according to claim 5, further comprising a stepof: (a) further diluting the topical composition in a separate step toprovide a composition containing at least about 95 wt. % water based onthe weight of the topical composition.
 7. A method according to claim 1,further comprising a step of: (a) adding surfactant to the topicalcomposition.
 8. A method according to claim 7, wherein the surfactantcomprises at least one of an ethoxylated surfactant, a propoxylatedsurfactant, an ethoxylated-propoxylated surfactant, and a mixturethereof.
 9. A method according to claim 1, wherein the compositioncomprises between about 30 wt. % and about 45 wt. % water.
 10. A methodaccording to claim 1, wherein the composition comprises between about 3wt. % and about 10 wt. % of the hydrophilic polymer composition andbetween about 30 wt. % and about 50 wt. % of the hydrophobic polymercomposition.
 11. A method according to claim 1, wherein the topicalcomposition comprises between about 70 wt % and about 96 wt. % water.12. A method according to claim 1, wherein the hydrophobic polymercomposition comprises a mixture of at least two differentpoly(vinylpyrrolidone/alkylene) polymers, wherein the alkylene group ofeach polymer contains at least about 10 carbon atoms.
 13. A methodaccording to claim 1, wherein the hydrophilic polymer compositioncomprises at least one of: (a) polyacrylic acid having a weight averagemolecular weight of at least about 50,000 and exhibiting less than 1%cross-linking; (b) poly(maleic acidlmethylvinylether) copolymer having aweight average molecular weight of at least about 50,000; (c) starch;(d) derivatives of starch; (e) cellulose; (f) derivatives of cellulose;(g) carboxymethyl cellulose; (h) polyvinyl alcohol; (i) cyclodextrins;(j) dextrans; and (k) mixtures thereof.
 14. A method according to claim1, wherein the hydrophilic polymer composition comprises polyacrylicacid having a weight average molecular weight of between about 50,000and about 4,000,000 and exhibiting less than 1% cross-linking.
 15. Amethod according to claim 1, wherein the hydrophilic polymer compositioncomprises poly(maleic acid/methylvinylether) copolymer having a weightaverage molecular weight of between about 50,000 and about 4,000,000.16. A method according to claim 1, wherein the composition furthercomprises between about 0.5 wt. % and about 5 wt. % surfactant.
 17. Amethod according to claim 16, wherein the surfactant comprises at leastone of an ethoxylated surfactant, a propoxylated surfactant, anethoxylated-propoxylated surfactant, and a mixture thereof.
 18. A methodfor manufacturing a topical composition precursor comprising meltprocessing a mixture comprising: (a) hydrophobic polymer compositioncomprising poly(vinylpyrrolidone/alkylene) polymer, wherein the alkylenegroup contains at least about 10 carbon atoms; (b) hydrophilic polymercomposition comprising at least one of: (i) polyacrylic acid having aweight average molecular weight of at least about 50,000 and exhibitingless than 1% cross-linking; (ii) poly(maleic acid/methylvinylether)copolymer having a weight average molecular weight of at least about50,000; (iii) starch; (iv) derivatives of starch; (v) cellulose; (vi)derivatives of cellulose; (vii) carboxymethyl cellulose; (viii)polyvinyl alcohol; (ix) cyclodextrins; (x) dextrans; (xi) mixturesthereof; and (c) wherein the functional group parity of the hydrophobicpolymer composition and the hydrophilic polymer composition is providedat a ratio of between about 1:1 and 5:1, and the topical compositionprecursor contains less than about 1 wt. % water.
 19. A method accordingto claim 18, wherein the hydrophobic polymer composition comprises atleast different poly(vinylpyrrolidone/alkylene) polymers, wherein thealkylene group of each polymer contains at least about 10 carbon atoms.20. A method according to claim 19, wherein the at least two differentpoly(vinylpyrrolidone/alkylene) polymers comprises a firstpoly(vtnylpyrrolidone/alkylene) polymer and a secondpoly(vinylpyrrolidone/alkylene) polymer, wherein the firstpoly(vinylpyrrolidone/alkylene) polymer is provided at a concentrationof between about 5 wt. % and about 54 wt. %, based on the weight of thehydrophobic polymer composition.
 21. A method according to claim 18,wherein the hydrophilic polymer composition comprises polyacrylic acidhaving a weight average molecular weight of between about 50,000 andabout 4,000,000.
 22. A method according to claim 18, wherein thepoly(maleic acid/methylvinylether) copolymer has a weight averagemolecular weight of between about 50,000 and 4,000,000.
 23. A methodaccording to claim 18, wherein the poly(vinylpyrrolidone/alkylene)polymer comprises poly(vinylpyrrolidone/1-eicosene).
 24. A methodaccording to claim 18, wherein the poly(vinylpyrrolidone/alkylene)polymer comprises poly(vinypyrrolidone/hexadecene).
 25. A methodaccording to claim 18, wherein the functional group parity of thehydrophobic polymer composition to the hydrophilic polymer compositionis provided at a ratio of between about 1.5:1 and about 3:1.
 26. Amethod according to claim 18, wherein the hydrophobic polymercomposition is provided at a concentration of between about 72 wt. % andabout 98 wt. %, and the hydrophilic polymer composition is provided at aconcentration of between about 2 wt. % and about 25 wt. %, based on theweight of the topical composition precursor.